This project was concluded last year. We previously reported that protective immunity can be generated in vaccinia-naive as well as vaccinia-immune macaques by immunization with recombinant vaccinia virus expressing SIVmne envelope glycoprotein gp160, followed by booster immunizations with gp160 protein. Animals were followed for up to 5 years after challenge to determine the clinical outcome of infection and the effects of immunization. Both E11S and uncloned SIVmne virus showed pathogenic potential in M. fascicularis. However, infection with the uncloned virus resulted in a more rapid disease course than E11S. Among animals infected with the uncloned virus, there was a significant delay of the onset of CD4 cell decline in immunized animals compared with the controls (95.0q15.4 wk for the immunized animals vs. 41.0q12.3 for the controls). However, there was no significant difference between the immunized and the control animals in the number that required euthanasia due to AIDS (2/10 vs. 5/10), nor the mean survival time among those that developed AIDS. So far, all surviving animals have low viral load and are positive only by PCR analysis, consistent with the notion that reduced viral load correlates with long-term survival. Therefore, in the absence of sterilizing immunity, reduction of viral load may be a desirable endpoint for vaccination.